Necrotizing Soft Tissue Infections - Complicated Skin Infections

Diagnosis

Indications for Testing

• Appropriate clinical presentation in addition to a high level of suspicion for the disease

Laboratory Testing

• Simple infections
  • Gram stain of aspirates or tissue biopsies – may not be as helpful as culture, depending on organism involved and quality of specimen
  • Cultures of tissue, wound
• More complicated infections (fever, tachycardia, immunocompromised patients)
  • CBC – elevated white cell count >15,000/mm³ with neutrophil predominance (left shift) frequently noted
  • Cultures of tissue, wound crucial
  • Blood cultures – infrequently positive but helpful for organism identification
  • C-reactive protein
  • Use of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score – ≥6 points has positive predictive value of 92% and negative predictive value of 96% for necrotizing fasciitis
  • Laboratory Risk Indicator for Necrotizing Fasciitis

    Laboratory Risk Indicator  for Necrotizing Fasciitis
    Variable, Units	Score
    C-reactive protein, mg/L
    <150	0
    ≥150	4
    Total white cell count, per mm3
    <15	0
    15-25	1
    >25	2
    Hemoglobin, g/dL
    >13.5	0
    11-13.5	1
    <11	2
    Sodium, mmol/L
    ≥135	0
    <135	2
    Creatinine, µmol/L
    ≤141	0
    >141	2
    Glucose, mmol/L
    ≤10	0
    >10	1
    Maximum score is 13.  A score of ≥6 should raise the suspicion of necrotizing fasciitis.  A score of ≥8 is strongly predictive of this disease.

• If above studies do not confirm necrotizing fasciitis, surgical exploration of the site may confirm the disease

Imaging Studies

• X-ray – subcutaneous air in tissue noted in about 25% of patients
  • May reveal foreign body in infected wounds
• US/CT/MRI – choose imaging study based on suspected location of infection and usefulness of study for site infected
  • Imaging frequently used for localized drainage of identified site

Differential Diagnosis

• Local infections (furuncles, cellulitis, abscesses, etc.)
• Insect and spider bites
• Fungal (Candida) septicemia
• Allergic reaction
• Crystalline arthritis
• Tenosynovitis (associated with inflammatory arthropathy)

Clinical Background

Aggressive soft tissue infections can cause extensive local tissue damage as well as systemic toxicity. These infections require prompt recognition in order to prevent severe morbidity and mortality.

Epidemiology

• Incidence – 4/100,000
• Age – usually occurs in older patients
• Sex – M:F, equal 
  • Exception in Vibrio vulnificus, M>F
• Transmission – skin entry via break in dermis (usual route)

Classification

• Gangrene
• Necrotizing fasciitis/cellulitis
• Myositis/myonecrosis
• Complicated/deep abscesses
• Infected burns/surgical wounds
• Toxin-mediated – toxic shock syndrome, staphylococcal scalded skin syndrome

Organisms

• Single organism common in uncomplicated infections; polymicrobic/synergistic more prominent in complicated infections
  • Staphylococcus spp (including methicillin-resistant Staphylococcus aureus[MRSA]), enterococci, Pseudomonas aeruginosa, Streptococcus spp, Enterobacteriaceae, Bacteroides spp, Proteus spp, Clostridium spp
    • Most common – Staphylococcus aureus, Streptococcus spp
  • Aerobic and anaerobic organisms frequently found in combination

Risk Factors

• Diabetes mellitus
• Alcoholism
• Immunocompromised state
• Liver disease
• Peripheral vascular disease
• Obesity
• Trauma
• Burns
• Age >50 years

Clinical Presentation

• General symptoms
  • Skin – erythema, tense edema, vesicles or bullae, necrosis ulcers, crepitus, gray or discolored wound drainage, pain extending past margin of skin infection
  • Constitutional – fever, diaphoresis, delirium, tachycardia, tachypnea
  • Most common locations – extremities (50-55%), perineum/buttocks (20%), trunk (18-20%), head and neck (8-10%)
• Clinical markers that may help differentiate necrotizing infection from localized infection include the following
  • Pain disproportionate to appearance of infection 
  • Crepitus
  • High fever
  • Rapidly spreading erythema
• Organisms and clinical scenarios/presentations

  Organism	Common Clinical Scenario	Most Common Underlying Comorbid Illnesses	Clinical Presentation	Prevalence
  Group A Streptococcus species	Skin abrasion, trauma, recent skin infection (herpes zoster, varicella-zoster, herpes simplex), human bite, intravenous/ subcutaneous drug abuse	Diabetes, cancer, alcoholism, stasis dermatitis, eczema	Intense erythema, edema and pain, lymphadenopathy, hemorrhagic and necrotic bullae, muscle myositis, erysipelas, impetigo; type II necrotizing fasciitis	One of the two most common monomicrobial infectious agents
  Peptostreptococcus and gram-negative	Colorectal or genitourinary disease; orofacial surgery, dental work	Older patients	Scrotal edema and perineal gangrene (Fournier gangrene), submandibular space (Ludwig angina)	Usually found in association with other organisms
  Staphylococcus aureus	Skin trauma, recent hospitalization or surgery, intravenous/ subcutaneous drug abuse	Obesity, diabetes, immunocompromising condition, eczema, rheumatologic diseases	Furuncles, local abscesses, diffuse macular erythroderma, pyomyositis, toxic shock syndrome, staphylococcal scalded skin syndrome	One of the most common agents of soft tissue skin infections
  Polymicrobial – often beta hemolytic streptococci with S. aureus (including MRSA), S. epidermidis or gram-negative bacteria such as E. coli, Proteus mirabilis, Klebsiella pneumoniae	Diabetic foot ulcer, recent surgery with purulent wound	Diabetes, immunocompromising condition, vascular disease (particularly lower extremity disease)	Moist gangrene with a foul odor, suppurative-necrotic ulcer surrounded by concentric zones of red cellulitis (Meleney gangrene), deeper abscess, type I necrotizing fasciitis	Most common presentation (>50% of all necrotizing soft tissue infections)
  Pseudomonas species	Bacteremia, moist skin infection, severe burn, recent hospitalization	Immunocompromising condition, diabetes	Hemorrhagic and necrotic bullae
  Vibrio vulnificus	Exposure to raw or undercooked seafood or exposure to seawater	Underlying liver disease, immunocompromising condition	Hemorrhagic and necrotic bullae, ecchymoses	Unusual in immunocompetent patients
  Clostridium perfringens	Severe trauma with wound contamination, recent surgery, intravenous drug abuse	None	Pale skin, edema, hemorrhagic and necrotic bullae, foul-smelling discharge, gas formation	Usually found in association with local tissue injury
  Pasteurella multocida	Cat or dog bite	None	Erythema, edema, serosanguineous discharge, lymphadenitis, tenosynovitis	Typically associated with animal bite
  Aspergillus, Mucor, Rhizopus	Traumatic wounds or burns	Immunocompromising condition	Erythema, severe pain, hemorrhagic bullae	Rarely occurs in immunocompetent patients
  Aeromonas hydrophila	Exposure to fresh water, skin abrasion	Usually none; sometimes an immunocompromising condition	Erythema, bullae, necrosis, possible gas formation	Unusual in immunocompetent patients

Treatment

• Initiate antibiotic therapy appropriate for polymicrobial infections; change therapy to match culture results
• Aggressive wound care, including wide-area surgical debridement
  • Necrotizing wounds are commonly fatal if not treated within 72 hours

Prevention

• Vibrio – do not eat raw seafood; avoid exposing open wounds to seawater
• Pasteurella – prophylaxis started at time of bite for serious bite wounds

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Clostridium botulinum culture	ARUP recommends contacting your local or state health department in suspected botulism cases If local and state officials are not available, the CDC can be contacted